1. A GC-FID method for quantitative analysis of N,N-carbonyldiimidazole
Claire Lee, Ian Mangion J Pharm Biomed Anal. 2016 Mar 20;121:1-5. doi: 10.1016/j.jpba.2015.12.028. Epub 2015 Dec 21.
N,N-Carbonyldiimidazole (CDI), a common synthetic reagent used in commercial scale pharmaceutical synthesis, is known to be sensitive to hydrolysis from ambient moisture. This liability demands a simple, robust analytical method to quantitatively determine reagent quality to ensure reproducible performance in chemical reactions. This work describes a protocol for a rapid GC-FID based analysis of CDI.
2. Derivatization and determination of residual N,N-Carbonyldiimidazole by LC for an in-process control test
Amaris Borges-Muñoz, Harshkumar Patel, Peter Tattersall J Pharm Biomed Anal. 2022 Jan 5;207:114395. doi: 10.1016/j.jpba.2021.114395. Epub 2021 Sep 28.
For the robust analysis of N,N-Carbonyldiimidazole (CDI), its derivatization into a more stable compound may be needed. Herein, the reaction of CDI with N-benzylmethylamine followed by LC-UV quantitative analysis was explored. Reaction conditions as well as LC method feasibility were demonstrated by qualification of selectivity from other impurities and reagents, linearity across a range of 0.05-0.15%w/w, spike and recovery across a range of 0.05-0.15%w/w, reaction reproducibility with various samples, reagents and analytical chemists, and sample stability of over 24 h. Rapid and quantitative derivatization of residual CDI was achieved at 0.1% w/w relative to the synthetic product under consideration. A fit-for-purpose limit test using a RPLC-UV method as an in-process control for the reaction completion of product, at scale, was successfully implemented and executed.
3. N,N'-Carbonyldiimidazole-mediated functionalization of superparamagnetic nanoparticles as vaccine carrier
Jenny Ho, Fatin M Nawwab Al-Deen, Aswan Al-Abboodi, Cordelia Selomulya, Sue D Xiang, Magdalena Plebanski, Gareth M Forde Colloids Surf B Biointerfaces. 2011 Mar;83(1):83-90. doi: 10.1016/j.colsurfb.2010.11.001. Epub 2010 Nov 5.
Particulates with specific sizes and characteristics can induce potent immune responses by promoting antigen uptake of appropriate immuno-stimulatory cell types. Magnetite (Fe(3)O(4)) nanoparticles have shown many potential bioapplications due to their biocompatibility and special characteristics. Here, superparamagnetic Fe(3)O(4) nanoparticles (SPIONs) with high magnetization value (70emug(-1)) were stabilized with trisodium citrate and successfully conjugated with a model antigen (ovalbumin, OVA) via N,N'-carbonyldiimidazole (CDI) mediated reaction, to achieve a maximum conjugation capacity at approximately 13 microgmicrom(-2). It was shown that different mechanisms governed the interactions between the OVA molecules and magnetite nanoparticles at different pH conditions. We evaluated as-synthesized SPION against commercially available magnetite nanoparticles. The cytotoxicity of these nanoparticles was investigated using mammalian cells. The reported CDI-mediated reaction can be considered as a potential approach in conjugating biomolecules onto magnetite or other biodegradable nanoparticles for vaccine delivery.
